This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein or a papilloma virus genome. This invention also relates to proteins coded by the papilloma virus genome and antibodies directed against them as well as their use in diagnosis, therapy and vaccination.
It is known that papilloma viruses infect the epithelium of human beings and animals. Human papilloma viruses (hereinafter referred to as HP viruses) are found in benign epithelial neoplasms, e.g. warts, condylomas in the genital zone, and malignant epithelial neoplasms, e.g. carcinomas of the skin and the uterus (cf. Zu Hausen, H., Biochimica et Biophysica Acta (BBA) 1288, (1996), pp. 55-78). HP viruses are also considered for the growth of malignant tumors in the oropharyngeal zone (cf. Zur Hausen, H., Curr. Top. Microbiol. Immunol. 78, (1977), pp. 1-30).
Papilloma viruses have an icosahedral capsid without envelope in which a circular, double-stranded DNA molecule of about 7900 bp is present. The capsid comprises a major capsid protein (L1) and a minor capsid protein (L2). Both proteins, coexpressed or L1 expressed alone, result in vitro in the formation of virus-like particles (cf. Kirnbauer, R. et al., Journal of Virology, (1993), pp. 6929-6936.
Papilloma viruses cannot be proliferated in monolayer cell culture. Therefore, their characterization is extremely difficult, the detection of papilloma viruses already creating considerable problems. This applies particularly to papilloma viruses in carcinomas of the skin.
Thus, it is the object of the present invention to provide a product by which papilloma viruses can be detected, particularly in carcinomas of the skin. Furthermore, a product should be provided to be able to take therapeutic steps against these papilloma viruses.
According to the invention this is achieved by providing the subject matters in the claims.
Therefore, the subject matter of the invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein (L1), the peptide comprising the amino acid sequence of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, or FIG. 6 (SEQ ID NOS: 2, 4, 6, 8, 10 or 12, respectively) or an amino acid sequence differing therefrom by one or more amino acids.
A further subject matter of the invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein, the DNA comprising the base sequence of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, or FIG. 6, (SEQ ID NOS: 1, 3, 5, 7, 9, or 11, respectively) or a base sequence differing therefrom by one or more base pairs.
FIG. 1 shows the base sequence and the amino acid sequence (SEQ ID NOS: 1 and 2, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL416 with DSM (Deutsche Sammlung von Miroorganismen und Zellkulturen [German-type collection of microorganisms and cell cultures]) under DSM 12309 on Jul. 14, 1998.
FIG. 2 shows the base sequence and the amino acid sequence (SEQ ID NOS: 3 and 4, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL428 with DSM under DSM 12310 on Jul. 14, 1998.
FIG. 3 shows the base sequence and the amino acid sequence (SEQ ID NOS: 5 and 6, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL463 with DSM under DSM 12311 on Jul. 14, 1998.
FIG. 4 shows the base sequence and the amino acid sequence (SEQ ID NOS: 7 and 8, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL473 with DSM under DSM 12312 on Jul. 14, 1998.
FIG. 5 shows the base sequence and the amino acid sequence (SEQ ID NOS: 9 and 10, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid KG80 with DSM under DSM 12313 on Jul. 14, 1998.
FIG. 6 shows the base sequence and the amino acid sequence (SEQ ID NOS: 11 and 12, respectively), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid TN111 with DSM under DSM 12314 on Jul. 14, 1998.